Viral and symptom rebound following anti-SARS-CoV-2 monoclonal antibody therapy in a randomized placebo-controlled trial.

We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.5 log10 copies/mL increase from day 3 or 7, and symptom rebound as hospitalization or any moderate/severe symptom for ≥2 days after initial symptom improvement. There was no difference in viral rebound (∼5%/arm) (analysis population n=713) or symptom rebound among participants who initially improved (hazard ratio 0.95 (95% CI 0.52, 1.75, analysis population) n=574); <1% had both viral/symptom rebound.

Real-world evaluation of early remdesivir in high-risk COVID-19 outpatients during Omicron including BQ.1/BQ.1.1/XBB.1.5.

BACKGROUND: A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. METHODS: We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. RESULTS: Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23-0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03-1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19-2.41]), BA.4/5 (0.50[95% CI 0.50-1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08-0.57]. CONCLUSION: Among outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.

Long-term cardiovascular health status and physical functioning of nonhospitalized patients with COVID-19 compared with non-COVID-19 controls.

Coronavirus disease 2019 (COVID-19) is reported to have long-term effects on cardiovascular health and physical functioning, even in the nonhospitalized population. The physiological mechanisms underlying these long-term consequences are however less well described. We compared cardiovascular risk factors, arterial stiffness, and physical functioning in nonhospitalized patients with COVID-19, at a median of 6 mo postinfection, versus age- and sex-matched controls. Cardiovascular risk was assessed using blood pressure and biomarker concentrations (amino-terminal pro-B-type-natriuretic-peptide, high-sensitive cardiac troponin I, C-reactive protein), and arterial stiffness was assessed using carotid-femoral pulse wave velocity. Physical functioning was evaluated using accelerometry, handgrip strength, gait speed and questionnaires on fatigue, perceived general health status, and health-related quality of life (hrQoL). We included 101 former patients with COVID-19 (aged 59 [interquartile range, 55-65] yr, 58% male) and 101 controls. At 175 [126-235] days postinfection, 32% of the COVID-19 group reported residual symptoms, notably fatigue, and 7% required post-COVID-19 care. We found no differences in blood pressure, biomarker concentrations, or arterial stiffness between both groups. Former patients with COVID-19 showed a higher handgrip strength (43 [33-52] vs. 38 [30-48] kg, P = 0.004) and less sleeping time (8.8 [7.7-9.4] vs. 9.8 [8.9-10.3] h/day, P < 0.001) and reported fatigue more often than controls. Accelerometry-based habitual physical activity levels, gait speed, perception of general health status, and hrQoL were not different between groups. In conclusion, one in three nonhospitalized patients with COVID-19 reports residual symptoms at a median of 6 mo postinfection, but we were unable to relate these symptoms to increases in cardiovascular risk factors, arterial stiffness, or physical dysfunction.NEW & NOTEWORTHY We examined cardiovascular and physical functioning outcomes in nonhospitalized patients with COVID-19, at a median of 6 mo postinfection. When compared with matched controls, minor differences in physical functioning were found, but objective measures of cardiovascular risk and arterial stiffness did not differ between groups. However, one in three former patients with COVID-19 reported residual symptoms, notably fatigue. Follow-up studies should investigate the origins of residual symptoms and their long-term consequences in former, nonhospitalized patients with COVID-19.

Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics.

BACKGROUND: Brain 18F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics. METHODS: We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics. RESULTS: Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r = - 0.44, p = 0.02) and with the duration of symptoms (r = - 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters. CONCLUSION: Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.

The Value of Lung Ultrasound to Detect the Early Pleural and Pulmonary Pathologies in Nonhospitalized COVID-19-Suspected Cases in a Population With a Low Prevalence of COVID-19 Infection: A Prospective Study in 297 Subjects.

OBJECTIVES: This prospective study aimed to evaluate the value of B-mode lung ultrasound (LUS) for the early diagnosis of coronavirus disease 2019 (COVID-19) infection in nonhospitalized COVID-19 suspected cases in a population with a low prevalence of disease. METHODS: From April 2020 to June 2020, in an ambulatory testing center for COVID-19-suspected cases, 297 subjects were examined by LUS before a nasopharyngeal swab was taken for a reverse transcription polymerase chain reaction (RT-PCR) test. The following LUS findings were defined as pathological ultrasound findings and were analyzed: the presence of 1) pleural effusion, 2) B-lines, 3) fragmented visceral pleura, 4) consolidation, and 5) air bronchogram in the consolidation. The LUS findings were compared with the RT-PCR test results. RESULTS: The result of the RT-PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive in 11 and negative in 286 subjects, and the prevalence of COVID-19 infection in the study participants was 3.7%. On LUS, a pathological finding could be detected in 56/297 (18.9%) study participants. The LUS revealed a sensitivity of 27.3%, a specificity of 81.5%, a positive predictive value of 5.4%, a negative predictive value of 96.7%, and a diagnostic accuracy of 79.9% for the identification of COVID-19 infection. CONCLUSIONS: For the identification of COVID-19 infection, LUS is highly sensitive to the patient spectrum and to the prevalence of the disease. Due to the low diagnostic performance in nonhospitalized COVID-19 cases in low-prevalence areas, LUS cannot be considered to be an adequate method for making a diagnosis in this group.

Treatment Options for Patients With Mild-to-Moderate Coronavirus Disease 2019 in Korea.

The coronavirus disease 2019 (COVID-19) continues to threaten public health in Korea although several surges have passed in the past 3 years since 2019. Although patients with mild-to-moderate COVID-19 can usually recover at home, antiviral therapy to prevent disease progression and hospitalization is beneficial for those at high risk of progressing to severe COVID-19. The purpose of this article was to review how antivirals have been rolled out for the treatment of COVID-19 and how domestic and international guidelines for their use have evolved. Several evidence-based treatment guidelines have been developed in Korea, including those derived from domestic studies. Although many different antiviral agents were nominated as promising therapeutics at the onset of the pandemic, most failed to show efficacy in clinical trials. Currently, three types of antiviral agents-nirmatrelvir-ritonavir, molnupiravir, and remdesivir-are available in Korea to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Each antiviral has its advantages and disadvantages. For most individuals, nirmatrelvir/ritonavir is preferred because of its high efficacy and convenience of administration. When serious drug interactions occur or are expected with nirmatrelvir/ritonavir administration, 3 days of remdesivir treatment is shown to be a reasonable alternative. Molnupiravir may be prescribed with caution only if no other therapeutic options are available or acceptable.

[Mild SARS-CoV-2 infection in vulnerable patients: implementation of a clinical pathway for early treatment]. / Infección leve por SARS-CoV-2 en pacientes vulnerables: implantación de una vía clínica de tratamiento precoz.

INTRODUCTION: The objective of this report is to describe the clinical pathway for early treatment of patients with acute SARS-CoV-2 infection and to evaluate the first results of its implementation. METHODS: This is a descriptive and retrospective study of the implementation of a clinical pathway of treatment in outpatients (January 1 to June 30 2022). Clinical pathway: detection and referral systems from Primary Care, Emergency services, hospital specialities and an automated detection system; clinical evaluation and treatment administration in the COVID-19 day-hospital and subsequent clinical follow-up. Explanatory variables: demographics, comorbidity, vaccination status, referral pathways and treatment administration. OUTCOME VARIABLES: hospitalization and death with 30 days, grade 2-3 toxicity related to treatment. RESULTS: Treatment was administered to 262 patients (53,4% women, median age 60 years). The treatment indication criteria were immunosupression (68,3%), and the combination of age, vaccination status and comorbidity in the rest47,3% of the patients s received remdesivir, 35,9% nirmatrelvir/ritonavir, 13,4% sotrovimab and 2,4% combined treatment with a median of 4 days after symptom onset. Hospital admission was required for 6,1% of the patients, 3,8% related to progression COVID-19. No patient died. Toxicity grade 2-3 toxicity was reported in 18,7%, 89,8% dysgeusia and metallic tasted related nirmatrelvir/ritonavir. Seven patients discontinued treatment due to toxicity. CONCLUSION: The creation and implementation of a clinical pathway for non-hospitalized patients with SARS-CoV-2 infection is effective and it allows early accessibility and equity of currently available treatments.

Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Efficacy and safety of ivermectin for treatment of non-hospitalized COVID-19 patients: A systematic review and meta-analysis of 12 randomized controlled trials with 7,035 participants.

INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.

Hospitalization Endpoint in Clinical Trials of Outpatient Settings: using Anti-SARS-COV-2 Therapy as an Example.

Purpose: In response to the COVID-19 pandemic, the World Health Organization (WHO) developed a set of outcome measures for trials primarily aimed at hospitalised patients. However, a gap exists in defining outcome standards for non-hospitalised patients. Therefore, this study aims to discuss hospitalisation as a primary outcome in outpatient trials and its potential pitfalls, specifically focusing on trials related to anti-SARS-COV-2 therapy. Methods: In this narrative review, researchers thoroughly searched MEDLINE and ClinicalTrials.gov from January 2020 to December 2022, targeting Phase III randomized controlled trials involving outpatients with mild-to-moderate COVID-19. The trials were specifically related to anti-SARS-COV-2 monoclonal antibodies or antiviral agents. The study collected essential data, including the type of intervention, comparator, primary objective, primary endpoint, and the use of estimands in the trial. Results: The search identified 12 trials that evaluated the efficacy of anti-SARS COV-2 therapies in a predefined population. Three studies used hospitalisation and death as primary endpoints in high-risk patients receiving monoclonal antibodies. Nine studies assessed the efficacy of several antiviral agents: four trials used hospitalisation and death as the main endpoints, while others used different measures such as virologic measures using the Reverse Transcription-Polymerase Chain Reaction test (RT-PCR), the eight-point WHO ordinal scale, symptom alleviation by Day 7 and time to clinical response. Conclusion: Choosing hospitalization as an endpoint may provide meaningful data such as the cost-effectiveness ratio of a drug. However, different hospital utilisation patterns and investigator decisions could bias clinical outcomes if no specific criteria are considered. Therefore, investigators should have clear criteria for determining variables that influence this measure.

Long-COVID-19 Impact in non-hospitalized patients: Sleep and quality of life 24 months after SARS-CoV-2 infection.

Background and Aims: Sleep disruption and reduced quality of life are common long coronavirus disease (COVID) manifestations, affecting survivors irrespective of initial COVID-19 severity. Limited research investigates symptoms beyond 24 months post-infection. We aimed to address this gap by longitudinally studying sleep patterns and overall quality of life in non-hospitalized adults, 24 months after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Methods: This prospective observational study involved the enrolment of 337 adult non-hospitalized patients in a consecutive fashion. Individuals with past COVID-19 (from 15 April 2020 to 30 June 2021) were examined at two Government hospitals and completed a telephone interview between 1 May 2023 and 30 June 2023, located in Jharkhand, India. Participants were queried about their sleep patterns and quality of life, utilizing the DSM5 LEVEL 2 and EQ-ED-5L tool, respectively. Results: Among 337 non-hospitalized participants, 212 completed the survey. Within this group (59.4% men, mean age 38), 36 (17.0%) experienced sleep impairment. All five dimensions of quality of life (QoL) were adversely affected in long COVID patients. Advanced age, high income, residing in rural or semi-urban areas, and having comorbidities were associated with a higher likelihood of decreased quality of life across various domains. Conversely, participants who were married, employed in healthcare or government positions, and vaccinated exhibited a reduced likelihood of experiencing lower quality of life. Conclusion: Long COVID-19 affects sleep and quality of life, with various demographic and clinical factors influencing outcomes. This study provides insights into the extended consequences of long COVID-19 and aids healthcare systems in addressing the challenges posed by this condition.

Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients.

Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVID biomarkers in non-hospitalized patients. Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers. The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.

Mild SARS-CoV-2 infection in vulnerable patients: implementation of a clinical pathway for early treatment.

INTRODUCTION: The objective of this report is to describe the clinical pathway for early treatment of patients with acute SARS-CoV-2 infection and to evaluate the first results of its implementation. METHODS: This is a descriptive and retrospective study of the implementation of a clinical pathway of treatment in outpatients (January 1 to June 30 2022). Clinical pathway: detection and referral systems from Primary Care, Emergency services, hospital specialities and an automated detection system; clinical evaluation and treatment administration in the COVID-19 day-hospital and subsequent clinical follow-up. Explanatory variables: demographics, comorbidity, vaccination status, referral pathways and treatment administration. OUTCOME VARIABLES: hospitalization and death with 30 days, grade 2-3 toxicity related to treatment. RESULTS: Treatment was administered to 262 patients (53,4% women, median age 60 years). The treatment indication criteria were immunosupression (68,3%), and the combination of age, vaccination status and comorbidity in the rest 47,3% of the patients s received remdesivir, 35,9% nirmatrelvir/ritonavir, 13,4% sotrovimab and 2,4% combined treatment with a median of 4 days after symptom onset. Hospital admission was required for 6,1% of the patients, 3,8% related to progression COVID-19. No patient died. Toxicity grade 2-3 toxicity was reported in 18,7%, 89,8% dysgeusia and metallic tasted related nirmatrelvir/ritonavir. Seven patients discontinued treatment due to toxicity. CONCLUSION: The creation and implementation of a clinical pathway for non-hospitalized patients with SARS-CoV-2 infection is effective and it allows early accessibility and equity of currently available treatments.

Self-Reported Persistent Symptoms at 18 Months and Above Among COVID-19 Non-hospitalized Patients: A Prospective Cohort Study.

INTRODUCTION: Since the beginning of the pandemic in early 2020, there have been numerous reports of symptoms that have lingered due to COVID-19. However, there is a lack of data concerning these persistent symptoms in non-hospitalized patients. This study sought to examine the prevalence of persistent symptoms at 18 months and beyond following the diagnosis of COVID-19 non-hospitalized patients. METHODS: A prospective cohort study comprised 212 non-hospitalized adult patients consecutively assessed from data available at tertiary care institutions through telephone interviews. During the interview, participants were routinely questioned about whether they were still experiencing any post-infection symptoms at the time of the study. RESULTS: Total 212 took part in the 18-month or longer follow-up survey. The most commonly reported symptoms during the acute phase were fever (n=149, 70.3%), weakness (n=118, 55.7%), and sore throat (n=100, 47.2%). At the 18-month and above follow-up, 167 patients (78.7%) reported at least one symptom continuing. The most common symptom at this time point was fatigue (n=109, 51.4%), followed by joint pain (n=57, 26.8%), and exertional dyspnea (24.5%). The possibility of symptoms returning after an 18-month follow-up and beyond was significantly lower in patients who had taken the COVID-19 vaccine (OR=0.29; 95% CI: 0.112-0.749; p=0.011) and those did not infect a second time (OR=0.232; 95% CI: 0.057-0.93; p=0.04). CONCLUSION: The present study reveals that clinical complications persist even at 18 months and beyond during follow-up, with a prevalence similar to earlier follow-up periods, regardless of the severity of the initial COVID-19 infection.

A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection.

OBJECTIVES: To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults. METHODS: This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes. RESULTS: RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (-0.837; 1.011), -0.10 (-2.171; 1.963), and -1.03 (-4.746; 2.682) log10 copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log10 copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively. DISCUSSION: Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (NCT03379675).

Physicians' Perception of Oral Nutritional Supplement Acceptance and Tolerability in Malnourished Outpatients: PerceptiONS Study.

Malnutrition is a common condition associated with various pathologies such as infections, neoplasms and digestive system disorders. Patients can be managed using different strategies, which include dietary modifications or oral nutritional supplements (ONS). It is important to promote good ONS adherence in order to attain clinical efficacy and cost-effectiveness. Several factors (amount, type, duration and tolerability) may have an impact on ONS adherence. PerceptiONS is a descriptive, cross-sectional observational study based on an ad hoc electronic survey designed to explore physicians' perception of malnourished outpatients prescribed ONS. The survey considered adherence, acceptance/satisfaction, tolerability and benefits within the context of Spain's healthcare system. The perceptions of 548 physicians regarding the experience of 2516 patients were analyzed. From the physicians' perspective, 57.11% of patients adhered to over 75% of the prescribed ONS. The organoleptic properties of ONS represented the aspect with the most positive impact on adherence, with smell (43.72%) ranking as the top characteristic. In general, patients were satisfied (90.10%) with the ONS, with their related benefits (88.51%) and their organoleptic properties (90.42%), and accepted ONS in their daily diet (88.63%). ONS improved patients' general condition (87.04%), quality of life (QoL) (81.96%) and vitality/energy (81.28%). Physicians would prescribe the same ONS again in 96.4% of the cases.

Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Methods: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome. Results: In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0-7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5-14.6]) and smell (OR, 11.2 [95% CI, 9.1-13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID. Conclusions: Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.

Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.

Background: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors. Methods: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I 2 index were used to evaluate heterogeneity in this meta-analysis. Results: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients. Conclusion: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

Real-world evaluation of bebtelovimab effectiveness during the period of COVID-19 Omicron variants, including BA.4/BA.5.

OBJECTIVES: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. METHODS: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. RESULTS: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P <0.001), as well as COVID-19-related hospitalization (1.0% vs 2.0%, adjusted odds ratio: 0.44 [95% confidence interval: 0.30-0.64], P <0.001). Bebtelovimab appeared to be more beneficial in lowering the odds of hospitalization among patients with two or more comorbidities (interaction P = 0.03). CONCLUSION: During the Omicron BA.2/BA.2.12.1/BA.4/BA.5 variant phase, bebtelovimab was associated with lower hospitalization.

Efficacy and Safety of Anti-SARS-CoV-2 Monoclonal Antibodies: An Updated Review.

Monoclonal antibodies (mAbs) had received emergency use authorization for mild-to-moderate coronavirus disease 2019 (COVID-19) or for prophylaxis against COVID-19, including casirivimab plus imdevimab (C+I), bamlanivimab plus etesevimab (B+E), tixagevimab plus cilgavimab (T+CG), and sotrovimab (S) and bebtelovimab (BEB). This systematic review was done to assess the efficacy and safety of the same. PubMed, Embase, Scopus, medRxiv, bioRxiv, and FDA fact sheets were searched for the studies published between January 2021 and May 2022, and appropriate search terms related to the mentioned mAbs were used for data collection. Review included original research including randomized clinical trials and observational studies published or preprints. Studies included in the review had compared with placebo or standard of care or no treatment or mAbs with each other and also of various doses. Data extraction was done and reviewed the same for both efficacy and safety. Total of 20 studies were included in this review. The rate of hospitalization within 30 days showed ∼2% in comparison to ∼7% with placebo. Significant reduction in viral load was more observed with combination mAbs. Combination therapy showed faster virological cure against the Gamma variant. With C + I as postexposure prophylaxis (PEP), 29.0% of asymptomatic participants developed symptomatic COVID-19. Pre-exposure prophylaxis with T+CG reduced the incidence of infection by 77%. Infusion-related reaction was the most common adverse event (AE). The neutralizing mAbs reduced hospitalization in mild-to-moderate patients with infusion-related reactions as common AE. The response was better in the seronegative patients. Most of these studies were conducted in unvaccinated individuals and against Alpha, Gamma, and Delta variants.